This application for a K23 Career Development Award is entitled "Genetic investigation of cognitive development in autistic spectrum disorders". The candidate has MD and PhD degrees. His PhD is in molecular neurodevelopment in genetic mouse models. His undergraduate training at MIT, and his MD in the Harvard-MIT Division of Health Sciences and Technology at Harvard Medical School involved studies in quantitative methods. The candidate has pursued clinical training through to Chief Residency in the MGH- McLean Psychiatry Residency. He is an Instructor in Psychiatry at Harvard Medical School with appointments at the MGH and Children's Hospital Boston, as well as a postdoctoral affiliation with the Broad Institute of MIT and Harvard. If successful, the career trajectory for this applicant is to lead a laboratory- based program in Molecular Psychiatry at MGH with a focus in autism and related disorders of cognitive development. Linked to this translational research lab, the candidate plans to direct a Clinical Research Program for Adults with Pervasive Development Disorders in MGH Psychiatry. The candidate's research proposal describes studies designed to identify genes in autism spectrum disorders (ASD). The candidate proposes to study two complementary patient populations: 1) a special founder population from the Arabic Middle East, Turkey and Pakistan, wherein parents of affected children are consanguineous; and 2) a large collection of North American families (>4000 samples) from AGRE and the Boston Autism Consortium, including a cohort of 200 families which the candidate proposes to characterized in MGH Pediatric Psychiatry. The consanguineous pedigrees will be enrolled as part of the Autism International Homozygosity Mapping Collaborative (for which the candidate serves as Associate Director) with the aim of discovering highly penetrant autosomal recessive genes. A principal tool for analysis will be the Affymetrix 500K SNP microarray, and studies will include genomic copy number, as well as deletion and homozygosity mapping. Genes thereby identified will be studied in the North American patients using large-scale resequencing, association studies and phenotype-genotype studies. Mentors include Chris A. Walsh, MD, PhD, Chair of Genetics at the Children's Hospital Boston and Director of the Boston Autism Consortium. Dr. Walsh's lab has expertise in international genetic collaborations and identifying recessive genes in neurodevelopmental and cognitive disorders. In addition, Mark J. Daly, PhD, a statistical geneticist at the Broad Institute will serve as co-mentor. The candidate is seeking training in human population and statistical genetics, and bioinformatics. He is also seeking patient- oriented research training in ASD which will be pursued through the Developmental Medicine Center at Children's Hospital, as well as with external autism research experts of national esteem. [unreadable] [unreadable] [unreadable]